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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study performed equivalent to OECD guideline.

Data source

Reference
Reference Type:
publication
Title:
Naphthalene Toxicity in CD-l Mice: General Toxicology and lmmunotoxicology
Author:
Shopp George M., White Kimber L. Jr., Holsapple Michael P., Barnes Donald W., Scherer Duke S., Anderson Alice C., Condie Lyman W. Jr., Hayes Johnnie R. and Borzelleca Joseph F.
Year:
1984
Bibliographic source:
FUNDAMENTAL AND APPLIED TOXICOLOGY 4, 406-419 (1984)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Acclimatisation period of test animals only 4 days instead of at least 5 days.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Naphthalene
- Source: Aldrich Chemical Company, Milwaukee, Wisconsin
- Substance type: organic, aromatic hydrocarbon
- Physical state: solid
- Analytical purity: pure, purity confirmed at 99.3% employing gas chromatography.
- Impurities (identity and concentrations): none reported
- Lot/batch No.: Lot No. EE09 1397

Test animals

Species:
mouse
Strain:
other: CD-1 ICR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass.
- Age at study initiation: 6 weeks
- Housing: in plastic cages with hardwood bedding (PWI Hardwood Sawdust, Lowville, N.Y.)
- Diet (e.g. ad libitum): Purina Rodent Chow No. 5001 (Ralston Purina Co., St. Louis, MO.) ad libitum
- Water (e.g. ad libitum): deionised water ad libitum
- Acclimation period: 4 days
- Fasting period: Mice were fasted for 18 hr prior to oral dosing, with food being returned 1 hr after dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%): 40-60%.
- Photoperiod (hrs dark / hrs light): light-dark cycle was maintained on 12-hr intervals

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
A corn oil (Mazola Pure Corn Oil, Best Food, Englewood Cliffs, N.J., Lot No. 6-0729) suspension of naphthalene was prepared daily and stirred continuously during dosing

VEHICLE
- Concentration in vehicle: Concentrations of the corn oil-naphthalene suspension were prepared such that all doses could be delivered in a volume of I0 ml/kg body wt.
- Vehicle: Mazola Pure Corn Oil, Best Food, Englewood Cliffs, N.J.
- Lot/batch no. (if required): Lot No. 6-0729
- Purity: pure
Doses:
Five dose levels (200, 400, 600, 800, 1000 mgjkg) were employed to determine the acute oral LD50.
No. of animals per sex per dose:
8
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The mice were continuously observed for 1 hr after dosing, hourly for the next 4 hr, and then twice each day for the next 14 days.
- Necropsy of survivors performed: yes All mice that died during the observation period and those that survived the 14-day period were necropsied.
Statistics:
All mice that died during the observation period and those that survived the 14-day period were necropsied. The LDIO, LDSO, and LD90 were computed for each sex by the Log Probit Analysis as described by Finney (1971).

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
710 mg/kg bw
Based on:
test mat.
95% CL:
> 584 - < 827
Sex:
male
Dose descriptor:
LD50
Effect level:
533 mg/kg bw
Based on:
test mat.
95% CL:
> 397 - < 659
Mortality:
The majority of the naphthalene-associated deaths occurred within the first 5 hr after dosing and all deaths occurred within the first 5 days.
Clinical signs:
With the exception of the low dose mice (200 mg/kg in males and 400 mg/kg in females) all mice developed ptosis with clear red secretions around the eye within 1 hr after dosing. Death followed depressed breathing and ataxia.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Naphthalene did not induce hemolytic anemia or cataract formation in CD 1 mice at the dosage levels employed. Male CD-1 mice (LD50 533 mg/kg body weight) are more susceptible to naphthalene than females (710 mg/kg body weight).
Executive summary:

An interesting finding in these studies was the lack of either naphthalene induced hemolytic anemia or cataract formation in CD 1 mice at the dosage levels employed. Both of these pathological lesions have been associated with human exposure to naphthalene.The acute toxicity data reported indicate that male CD-1 mice are more susceptible to naphthalene than females. Since little is known about the mechanisms associated with the acute toxicity of this compound, including whether the toxicity is associated with the parent compound or a metabolite, an understanding of the mechanisms responsible for the sex differences must await further investigation.

Naphthalene appears to be more toxic in mice when administered orally than parenterally.